PHARMACEUTICAL FORMULATIONS OF A BRUTON'S TYROSINE KINASE INHIBITOR
Described herein are pharmaceutical formulations of Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one. Also disclosed are methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
1 - 25 . (canceled)
26 . A method of treating a disease in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a high-load solid tablet formulation, wherein the high-load solid tablet formulation comprises at least 50% w/w ibrutinib.
27 . The method of claim 26 , wherein the disease is cancer.
28 . The method of claim 27 , wherein the cancer is a B-cell proliferative disorder.
29 . The method of claim 26 , wherein the disease is a hematological malignancy.
30 . A process for preparing a high-load solid tablet formulation comprising at least 50% w/w ibrutinib, wherein the process comprises a wet granulation method.
31 . The process of claim 30 , wherein the wet granulation method comprises granulating a mixture of ibrutinib and intragranular excipients with a granulation liquid to form granules.
32 . The process of claim 31 , wherein the intragranular excipients comprise microcrystalline cellulose and polyvinylpyrrolidone.
33 . The process of claim 31 , comprising (1) mixing ibrutinib with the intragranular excipients; (2) granulating the mixture of ibrutinib and the intragranular excipients with purified water or an aqueous binder solution to form granules; (3) drying the granules to form dried granules; (4) milling the dried granules; (5) blending the milled granules with the extragranular excipients; and (6) compressing the mixture of milled granules and the extragranular excipients to form tablets of the high-load solid tablet formulation.
34 . The process of claim 33 , wherein the intragranular excipients comprise microcrystalline cellulose and polyvinylpyrrolidone.
35 . The process of claim 33 , wherein the extragranular excipients comprise croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate.
36 . The process of claim 35 , wherein the extragranular excipients further comprise microcrystalline cellulose.
37 . The process of claim 36 , wherein the colloidal silicon dioxide is present in an amount from about 0.4% w/w to about 0.8% w/w.
38 . The process of claim 36 , wherein the magnesium stearate is present in an amount from about w/w 0.1% w/w to about 1.5% w/w.
39 . The process of claim 36 , wherein the magnesium stearate is present in an amount from about 0.01% w/w to about 2% w/w.
40 . The process of claim 36 , wherein the microcrystalline cellulose is present in an amount from about 1% w/w to about 10% w/w.
41 . The process of claim 36 , wherein the microcrystalline cellulose is present in an amount from about 5% w/w to about 20% w/w.
42 . The process of claim 36 , wherein the microcrystalline cellulose is present in an amount from about 8% w/w to about 20% w/w.
43 . The process of claim 36 , wherein the microcrystalline cellulose is present in an amount from about 8% w/w to about 15% w/w.
44 . A high-load solid tablet formulation comprising ibrutinib and one or more pharmaceutically acceptable excipients, wherein ibrutinib is a compound with the structure of Compound 1,
and wherein the high-load solid tablet formulation comprises at least 50% w/w of ibrutinib.
45 . A kit comprising the high-load solid tablet formulation of claim 44 , and instructions for use.